This project consists of a longitudinal, prospective study of the population-at-risk for osteoporosis. Research subjects are 1914 normal women who were aged 35-45 at the start of the study in 1967. Observations are made once every five years and consist of comprehensive personal, calcium kinetic, calcium metabolic, hormonal, and physiological measurements, as well as radiogrammetric and photon-densitometric measurement of bone mass. Well over 120 primary and derived variables are accumulated on each subject. The purposes of the project are: 1) to obtain comprehensive longitudinal data on various measures of calcium metabolism, bone metabolism, and related physiological functions in a group of untreated women from the perimenopausal period to the median onset time of osteoporotic symptoms; 2) to provide an exhaustive physiological profile both on women who develop symptomatic osteoporosis, and on those who do not, thereby allowing prospective characterization of the differences between them and of the factor influencing those differences; 3) to permit better identification of the osteoporosis-prone subset and thereby to provide both a rational basis for prophylactic treatment and the identification of subjects who should be its target; 4) to characterize cross-sectional inter-relationships between major physiological variables during this key era of osteoporosis development; and finally 5) to provide a comprehensive database for testing hypotheses about associations among variables developed by us and others outside the context of this proposal. The plan is to continue our observations on this cohort until a sufficient number develop osteoporosis-related fractures. At the onset of the new project period the study population will be in the age-range 58-68. Thirty-three probable fragility-related fractures have occurred in the cohort to date. We anticipate seeing substantially more such fractures developing during this next five-year period.